Recently, much attention has been paid to the role of selectin which is a cell adhesion molecule in various inflammatory diseases. For example, there have been known some kinds of selectin, e.g., E-selectin (occasionally referred to as ELAM-1), P-selectin (occasionally referred to as GMP-140), L-selectin (occasionally referred to as LECAM-1), etc., and these selectins are present on various cells in the progress of inflammatory response.
For example, E-selectin is an adhesion molecule which is mainly induced on the surface of vascular endothelial cells by stimuli with TNF.alpha. (tumor necrosis factor .alpha.), IL-1 (interleukin 1); P-selectin is an adhesion molecule which is mainly induced at platelet .alpha.-granules or Wiebel-Pallade corpuscle of vascular endothelial cells by the stimuli with thrombin, histamine, etc.; and L-selectin is an adhesion molecule which is present on the surface of leucocyte cells.
Generally, cell infiltration is one of the most important symptoms of inflammation, and it is known that white blood cells in the blood bind to the vascular endothelial cells, and then infiltrate into the affected tissue. Prior to the attachment of white blood cells to vascular endothelial cells, the white blood cells roll along the endothelium, which is called "rolling". The "rolling" is the important event as the first stage of cell infiltration, and it is mediated by the binding of the above-mentioned various selectins to sialyl Le.sup.X sugar chain (ligand of selectin) which is present on the surface of white blood cells.
Therefore, there have been tried treatments of various inflammatory diseases by blocking the binding of selectin to sialyl Le.sup.X oligosaccharide, and inhibiting adhesion of white blood cells. As a selectin ligand (counter ligand) inhibiting the adhesion of white blood cells, there are known peptide counter ligands (e.g., WO 95/04751, WO 95/10296, etc.) in addition to some sialyl Le.sup.X derivatives, and these ligands are compounds having only fucose as a sugar moiety.
Drugs containing a counter ligand of selectin as an active ingredient (selectin inhibitors) can suppress and control various inflammatory diseases such as inflammatory dermatitis (e.g., atopic dermatitis, contact hypersensitivity, photodermatosis, etc.), autoimmune chronic diseases (e.g. rheumatoid arthritis, chronic thyroiditis, etc.), and the like, by inhibiting the adhesion of white blood cells.
Besides, in case of ischemia-reperfusion injury, it has been reported that various selectins participate in the endothelial cell injures caused by neutrophil infiltration (cf., stroke, 25, 202-210 (1994)). In fact, it has been reported that ischemia-reperfusion injury in reflow animal models is suppressed by a sialyl Le.sup.X derivative which is a counter ligand of selectin (cf., J. Clin. Invest., 93, 1140-1148 (1994)!. Therefore, a selectin inhibitor can show inhibitory effects on ischemia-reperfusion injury as well (cf., U.S. Pat. No. 5,444,050).